Some conventional particle detection schemes are label-based and others are label-free. Label-based detection schemes involve labeling the target molecules. Labeling, for example, can be done by attaching a light emitting particle to the target molecule. On the other hand, in label-free detection schemes, some intrinsic property of the target molecule itself is detected, such as the target molecule's mass or charge.
Nanoscale devices are widely regarded as potential candidates for ultra-sensitive, label-free detection of bio-chemical molecules. Among the various technologies, much recent research has been devoted to mechanical and electrical biosensors. However, these technologies are plagued by many challenges in their path to further optimization. Consider, for example, mechanical biosensors such as nanocantilevers. FIG. 1(a) illustrates a conventional nanocantilever. Here, the capture of target molecules on the cantilever surface can modulate the cantilever's mass, stiffness, or introduce an additional surface stress. This change in mechanical properties of the cantilever can then be observed as a change in its resonance frequency or beam deflection. Detection schemes (like an optical detection scheme) utilize complex instrumentation to detect these changes in mechanical properties, which precludes them from many low cost, point-of-care applications. Further, the response of mechanical biosensors varies linearly with change in mass/surface stress of cantilevers, and, therefore, may often not be sensitive enough to detect target molecules at low concentrations at the early stages of onset of a disease.
On the other hand, conventional electrical biosensors (such as the ion-sensitive field-effect transistor (“ISFET”) illustrated in FIG. 1(b)) sense the modulation of gate surface potential due to the presence of charged biomolecules. These conventional electrical biosensors operate in a solution that contains, not only the charged target particles that are desired to be detected, but also other charged particles. Moreover, these conventional electrical biosensors use a reference electrode to keep the potential of the solution fixed for stable measurements. The presence of other charged particles in the solution screens the charge of the particles to be detected and is referred to as “electrostatic screening”. Electrostatic screening, therefore, hinders target particle detection sensitivity. In addition, electrical biosensors face an uphill challenge of miniaturization due to the use of their reference electrodes, especially for lab-on-chip applications. Further, electrical biosensors respond to charged biomolecules and, hence, are not suitable for detecting the presence of any non-charged particles.
Accordingly, a need exists in the art for improved label-free particle detection systems.